Submissions for variant NM_000138.5(FBN1):c.2638G>A (p.Gly880Ser)

dbSNP: rs794728194

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000556229	SCV000627860	pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 880 of the FBN1 protein (p.Gly880Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Marfan syndrome (PMID: 12402346, 15821637, 18435798, 22772377). ClinVar contains an entry for this variant (Variation ID: 200000). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects FBN1 function (PMID: 16905551). For these reasons, this variant has been classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769644	SCV000901045	likely pathogenic	Familial thoracic aortic aneurysm and aortic dissection	2019-01-25	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269745	SCV001449976	pathogenic	not provided	2019-11-13	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001269745	SCV001714511	pathogenic	not provided	2020-09-02	criteria provided, single submitter	clinical testing	PS3_moderate, PS4_moderate, PM1, PM2, PP1, PP2, PP3, PP4
Revvity Omics, Revvity	RCV001269745	SCV002023045	pathogenic	not provided	2020-10-03	criteria provided, single submitter	clinical testing
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand	RCV000663561	SCV004123080	pathogenic	Marfan syndrome	2023-07-01	criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000663561	SCV004805962	uncertain significance	Marfan syndrome	2024-03-25	criteria provided, single submitter	clinical testing
Center for Medical Genetics Ghent, University of Ghent	RCV000663561	SCV000786872	likely pathogenic	Marfan syndrome	2017-11-07	no assertion criteria provided	clinical testing